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- W2070036625 abstract "529 Increased c-fos synthesis in mononuclear cells from patients with corticosteroid resistant asthma SJ Lane MD PhD. IM Adcoek PhD*. PJ Barnes MD*. TH Lee MD UMDS, Guy's Hospital, London, UK and *National Heart & Lung Institute, London UK We have demonstrated increased AP-1/TRE binding and reduced GR/GRE binding in unstimulated mononuclear cells from corticosteroid resistant (CR) as opposed to corticosteroid sensitive (CS) asthmatic subjects which is secondary to an impaired specific AP-1/glucocorticoid receptor (GR) interaction which may reflect sequestration of the GR by AP1. We have measured c-fos mRNA from PBMC cultured in the presence and absence of PMA using quantitative RT/PCR and specific c-los transcription using a nuclear run-off assays in CS and CR asthmatic subjects. There was no difference in c-fos expression between the two groups in the absence of PMA. In both groups c-fos expression was maximal when stimulated with 10ng/ml PMA for 20 minutes. There was a 3-fold greater increase in peak c-los mRNA accumulation in the CR as opposed to the CR group which nuclear run-off assays demonstrated to be secondary to a 2.7-fold increase in c-fos synthesis. There was no difference in baseline c-Fos protein levels between the two groups, however there was a significant 1.7-fold increase in protein levels after 6-8 hours stimulation with PMA. We suggest that increased c-fos mRNA and protein synthesis may provide a mechanism underlying glucocorticoid resistance seen in these cells, in that excess AP-I may overcome the anti-inflammatory effects of a limited number of available GRs in any given cell. 531 N a s a l C o l d , D r y A i r ( C D A ) C h a l l e n g e R e s u l t s in S t r o n g e r N a s a l a n d P u l m o n a r y R e s p o n s e s in A s t h m a t i c s C o m p a r e d to P a t i e n t s w i t h Rhinitis L Stet~hens. D Proud PhD. and A Tobias MD. Bal t imore M D -This study was performed to address two questions: a) Is the nasal mucosa of patients with asthma and active rhinitis (AS/RH) more sensitive to CDA than that of patients with active rhinitis only (RH)? b) Does CDA nasal challenge induce pulmonary responses? Twenty four AS/RH and 22 RH patients (mean+SD FEVI % predicted: 82.3+14.5 and 97.9+11.1, respectively) were tested with CDA nasal provocation according to a previously established protocol. Monitoring of the nasal response included Symptom Scores (SSs) on 10era long visual analog scales, and measurement of histamine and lysozyme in nasal lavage fluids. Prior to, and at 5' and 15' after CDA provocation, PFTs were performed. Means+SEM of the changes from baseline for Pthe nasal response are shown below. *: p 0.3) group. Correlations between the CDA-induced changes in nasal outcomes and the changes in PFTs did not yield statistically significant results. We conclude that, compared to patients with RH, the nasal mucosa of AS/RII patients is more sensitive to CDA. This is in keeping with the fact that the lower airways of these populations are also different in their response to this stimulus. The mechanism by which nasal CDA reduces pulmonary function in the AS/RH group is unknown but this observation offers further support to the concept of nose-lung interaction. 530 Bronchial hyperresponsiveness (BHR) in patients with symptoms of gastroesophageal reflux disease (GERD). SG Hinze, D Rosemeyer, Bad Driburg~ Germany. The association between bronchial asthma and GERD is well established. The causal link of both events is still unclear. The purpose of this study was to examine a possible coincidence between BHR and GERD in patients without acute or chronic obstructive airway disease. 81 in-patients in our clinic were examined because of symptoms of GERD. All patients underwent esophagoscopy, 24h-pH-monitoring, and unspecific bronchial provocation test with acetylcholine. Additionally, blood gases were taken before and after bronchial challenge to verify a gas exchange disturbance. A GERD was diagnosed in 45 patients. Esophagitis was found in 20 cases (3 times with Barrett metaplasia). The median percentage of time the esophagus-pH was less than 4 amounted to 10.1% versus 3 % in patients without GERD (p< 0.0001). A peptic esophagus stricture was not seen. The reflux symptoms mentioned by the subjects did not correlate very well with the degree of GERD in endoscopy or esophagus-pH-metry. A BHR occurred more often in patients with GERD (55 %) than in those without (22 %) (p< 0.01). The mean decrease of FEV1 after bronchial provocation in patients with GERD was 23 % versus 15 % in patients without GERD (p< 0.05). In patients with GERD there was no significant correlation between the decrease of FEVt and P, O2 after bronchial challenge and the percentage of time that the esophagus-pH was less than 4, neither inflammatory signs of the lower esophagus. No patient suffered from coughing or wheezing during the study period. It can be concluded that although there is an increased incidence of BHR in patients with GERD, we have no evidence for a correlation between bronchial asthma and GERD in these subjects. The occurrence of esophagitis is not obligatorily for the development of BHR. 532 r h u M A b E 2 5 (E25) , h u m a n i z e d m u r i n e m o n o c l o n a l anti-IgE, i n h i b i t s t h e a l l e r g e n i n d u c e d e a r l y a s t h m a t i c r e s p o n s e (EAR) . D W C o c k c r o f t , S Ka l r a , R B h a g a t , V A Swys tun , L P B o u l e t , J C o t e , M L a v i o l e t t e , F D e s c h e s n e s , K R C h a p m a n , L D C l e l a n d , R B Fick , J Su, A D e V a u l t . S a s k a t o o n , Q u e b e c City, T o r o n t o , C a n a d a , S a n F r a n c i s c o , U S A . The effect of E25 on the concentration of allergen causing a 15% EAR (allergen PC15 ) was assessed in a multi-centre, doubleblind, parallel, l l -wk study. Ten allergic asthmatics received intravenous E25, 2 mg/kg on d 0, and 1 mg/kg on d 7,14,28,42,56 & 70, while 9 received placebo. The allergen PC15 was measured on d -1,27,55, & 77. The median change in allergen PCt5 in doubling doses (dd=A log PCt5+0.3) compared to d -1 is shown in the table. Median PC15 increased 2.2 to 2.7 doubling doses (range -0.6 to 4.8) after E25 (p < 0.002 vs. placebo). day 27 day 55 day 77 E25 2.3 dd 2.2 dd 2.7 dd Placebo -0.3 dd +0.1 dd -0.8 dd Methacholine PC20 (d-2,42,76) improved slightly only on d 76 (p=0.048) after E25. Mean serum free IgE fell by 87-91% after E25 and the fall appeared to correlate with effect on allergen PC15. There were no significant changes in allergen PCi5 , methacholine PC20 or free IgE after placebo. E25 shows great promise as a novel anti-aUergic treatment for asthma." @default.
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- W2070036625 title "529 Increased c-fos synthesis in mononuclear cells from patients with corticosteroid resistent asthma" @default.
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